Background and Objective: Alcohol use disorder (AUD) can be a treatable condition, but relapse rates are
still high and new therapeutic targets important to the pathophysiology need to be identified. Emerging pre-
clinical and human postmortem data implicate astroglia, the most abundant glial cell in brain, in AUD behavior
and associated brain damage. Although controversial, we believe that the astroglial response to chronic brain
insult (e.g., in AUD) is largely and normally protective (i.e., not harmful) by supporting neuronal metabolic
function and integrity. Since the status of astroglia in brain of persons with AUD is uncertain, and may even be
compromised, our overall Objective is to establish whether the astroglial cell is deficient, or not, in living brain
of persons with AUD. We expect that the obtained results will help guide therapeutic efforts.
Specific Aims and Hypotheses: We aim to establish whether brain levels of an astroglial marker, the enzyme
monoamine oxidase B (MAO-B), are lower in AUD than those in healthy control subjects (and may recover
during protracted abstinence). Our directional working hypothesis is based on some postmortem human
brain data suggesting that brain astroglial integrity might be lower than normal in AUD.
Design: To measure astroglial status we will measure binding of [11C]SL25.1188, a third generation PET
(positron emission tomography) radiotracer selective for MAO-B, which we recently developed for use in the
human. 25 persons with AUD in early abstinence (3-7 days) 15 of which are estimated to completed a scan
during protracted abstinence (~21 days) and 25 matched control subjects will be enrolled. We will also
examine the relationship between astroglial activation (inferred from PET data) and peripheral blood measures
of immune markers and explore whether these might be related to behaviour (e.g. relapse, craving,
Relevance: Our team is unique in combining extensive experience in measuring glial proteins in both
postmortem and living brain of persons with substance use disorders and in developing/using (to our
knowledge) the only third generation radiolabeled astroglial marker in human PET brain imaging investigations.
The obtained results will represent the first step in guiding therapeutic efforts targeted at the brain astroglial cell
in AUD while at the same time exploring the relationship between brain and peripheral (blood) markers in this
condition. The latter effort is innovative and will address the unmet need for identification of simple,
noninvasive and inexpensive pathophysiologically relevant peripheral biomarkers of CNS “damage”.